It is well known in the art that shellac is an excellent film former. Shellac has been used for tablet coating for a century. Shellac films give good performance when freshly deposited out of alcohol but they crosslink and esterify in the dried film and extend the release characteristics after six months or a year. This particular defect has led to reduction in the use of shellac for tablet coating. The FDA lists the excipients used in NDA products every four years, in 1988 shellac was used in 278 listings, in 1992, 219, in 1996 it was used in only 73 listings. Because of the problems with shellac its use has been declining for more than 30 years. Many patents and other references note shellac, but it is not promoted but only mentioned as a known and historically used material. The pharmaceutical industry has moved away from shellac as a significant resin for coating. Forty years ago it was the most popular resin for enteric coating; today it is hardly used. The invention herein discloses surprising and new methods to make shellac very useful again.
Many attempts have been made to overcome these defects but the best modification of shellac systems is to use shellac out of water instead of alcohol. Shellac is very soluble in alcohol and can be used in old conventional pans for coating. However shellac holds on to the last traces of alcohol as the film dries. Using erased shellac eliminates these traces of alcohol and prevents esterification of the shellac. Other additives can be added to prevent crosslinking and make shellac useful for tablet coating.
The growth of the food supplement industry has presented a new opportunity for shellac since it is a food approved resin. There is an interest in using shellac for the numerous needs the food supplement industry has for reliable coating systems. Films that can give delayed release, enteric release and colonic release are in great demand. Coating is also needed for sealing products and taste masking many of the products as well. There is no other resin that is so versatile as shellac. Many of the resins used in drug manufacturing can not be used for food supplement products.
Briefly and basically, in accordance with the present invention, a film coating and a method of making a film coating are disclosed that produce a controlled release profile in an environment having a selected pH based on the shellac of a preselected acid number.
In accordance with the present invention, films that release or dissolve at or above pH 7.4 are based on the selection of shellac with an acid number below 74. Films that release or dissolve above pH 7.0 are comprised of a shellac selected with an acid number below 80. Films that release or dissolve at below pH 7.0 are comprised of shellac selected to have an acid number above 80.
The film may be modified with a water soluble resin at from 5-50% by weight of the shellac content while still giving the same pH release profile. Presently preferred water soluble resins may be selected from the group consisting of hydroxypropyl methylcellulose (HPMC), methylcellulose (MC), hydroxypropylcellulose (HPC), polyvinyl pyrrolidone (PVP), modified starch or maltodextrin and natural gums such as acacia.
The film may be plasticized with the fatty acids at from about 10-20% by weight of the combined resin content and from about 5-20% by weight of a water soluble plasticizer to enhance the release profile of the film. The fatty acids may be oleic acid, stearic acid or other fatty acids. Oleic acid is presently preferred. The water soluble plasticizer may preferably be selected from the group consisting of glycerine, propylene glycol, polyethylene glycol (molecular weight 300-8000), triacetin (TA) and triethyl citrate.
Preferably, the shellac will comprise 50% or more of the resin system.
The invention further includes the method of producing a film coating having a controlled release profile such that it will release in an environment having a specified pH using the method of selecting a shellac having a predetermined acid value. The method includes adding water soluble resins and plasticizers and dyes and other colorants. The method further includes the method of producing a shellac having a predetermined acid value by using the step of blending shellacs of known different acid values to produce a shellac having an acid value of a predetermined value. The shellac is preferably deposited out of water, and not alcohol.
The present invention presents a method of using shellac that overcomes the defects and produces films that are useful and reliable. Several forms of shellac are available. Our interest will be directed to shellacs that are refined decolorized orange shellac with an acid number 68-73 and refined dewaxed bleached shellac with acid numbers 72-91. The shellacs of interest must meet the specification in the NF19. The acid number which is used in this disclosure is the acid value defined in the monograph and is mg. of KOH per gram of shellac. Formulating with shellac according to the acid number and the unique properties related to it will be the focus.
All the grades of shellac are compatible and can be blended to give resins of distinct acid number. We have found that shellac blends with acid numbers that are low dissolve in an environment having a high pH and those with high acid numbers dissolve in an environment having a low pH. Shellac with acid numbers 68-73 dissolves at pH above 7.4. Shellac with acid numbers 74-80dissolves at pH 7 and above. Shellac with acid numbers above 80 dissolves at pH less than 7.
Shellac is dissolved in water with the aid of ammonium carbonate, ammonium bicarbonate or ammonia at about 50-60xc2x0 C. The final solution will be clear at a pH above 7 and 10-30% solids of shellac. Shellac solids of known acid number are blended to give a desired acid number to the dissolved material. Alternatively shellacs of various acid number can be individually dissolved and the solutions blended to give the desired acid number to the mix.
With the shellac solutions as a starting base, formulations can be made for coating systems that meet any need for tablet coating, particle coating or encapsulation that is presented. The shellac coating of the present invention may be utilized in any type of pharmaceutical application including pellets, granules, tablets, capsules or any other pharmaceutical solid dosage form. Additionally, the shellac coating of the present invention may be utilized to coat various food supplements and other nutritional compositions. including, but not limited to, garlic; amino acids and various vitamins.
If the coating is to release in the colon, the film is based on shellac that dissolves above pH 7.4. If the coating is to meet the USP enteric release, the film will be based on a shellac that has an acid number of 81 or higher. Shellac resin is compatible with hydroxypropyl methylcellulose (HPMC), methylcellulose (MC), hydroxypropylcellulose (HPC), polyvinyl pyrrolidone (PVP), modified starch or maltodextrins and a variety of natural gums (acacia,etc.). These water soluble resins and any water soluble plasticizer can be formulated with shellac to give a film with the desired release characteristics. The plasticizers used may be glycerine, propylene glycol, polyethylene glycol (300-8000 MW), triacetin (TA), and triethyl citrate.
Also, plasticizers that are not soluble in water can be used in formulating. shellac systems. These plasticizers include castor oil, vegetable oils (corn, soy, etc.), acetylated monoglycerides, fatty acids, glyceryl monostearate and other glycerides and glycolates of fatty acids. When these plasticizers are used the coating solution is cloudy and requires stirring. Some materials derived from fatty acids can be ethoxylated to produce soluble plasticizers like polysorbate 80 which is very compatible with the shellac systems.
The resin systems formulated with HPMC and shellac have release characteristics surprisingly similar to straight shellac. However the coating process is easier to manage and produces an elegant film. MC slightly delays the release rate and PVP slightly increases the release rate compared to HPMC but most of the water soluble resins have little effect on the release rate, while improving the coating quality.
The flexibility of shellac to receive the large variety of additives listed gives rise to systems that can be formulated for precise pH release or to vary the rate of release at different pH values. The water based shellacs of various acid number give a starting composition of surprising versatility. Reliable and stable coatings are produced.
It is also to be noted that these systems can be formulated to receive any of the colors approved for use on foods and drugs. The incorporation of dyes and pigments can be tolerated to 50% of the resin level. There is no limit to lower quantity of color added but is determined by the desired color depth. Talc is also very compatible with the shellac systems.
The colors approved for use in foods and drugs may be any FDA approved colors, these include FDandC dyes and lakes, DandC dyes and lakes, titanium dioxide, iron oxide, natural colors and other materials such as talc, calcium carbonate and alumina. These colors may have some effect on the permeation of the film, but do not interfere with the release as controlled by the acid number of the shellac.
Based on shellac of varying acid number many formulations can be prepared to release at precise rates and pH. HPMC and most soluble resins and water soluble plasticizers have little effect on release but improve coating. MC slightly delays release and PVP slightly speeds up release. Oleic acid and other fatty acids improve coating and slightly lower the pH for release. Plasticizers insoluble in water like glyceryl monostearate slow the release slightly but improve the coating.